Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights.

Abstract

Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian carcinoma cells). Some compounds showed IC50 values < 0.3 μM. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC), V79 and L929 cells. Mechanistic role for

NAD(P)H:

Quinone Oxidoreductase 1 (NQO1) was also elucidated. These compounds could provide promising new lead derivatives for more potent anticancer drug development and delivery, and represent one of the most active classes of lapachones reported.

• Authors: Eduardo H G da Cruz, Molly A Silvers, Guilherme A M Jardim, Jarbas M Resende, Bruno C Cavalcanti, Igor S Bomfim, Claudia Pessoa, Carlos A de Simone, Giancarlo V Botteselle, Antonio L Braga, Divya K Nair, Irishi N N Namboothiri, David A Boothman, Eufrânio N da Silva Júnior
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 122 Pg. 1-16 (Oct 21 2016) ISSN: 1768-3254 [Electronic] France
• PMID: 27341379 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzoquinones
• Triazoles
• quinone
• Selenium

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology, toxicity)
• Benzoquinones (chemistry)
• Cell Death (drug effects)
• Cell Line, Tumor
• Chemistry Techniques, Synthetic
• Drug Design
• Humans
• Leukocytes, Mononuclear (drug effects)
• Oxidation-Reduction
• Selenium (chemistry)
• Structure-Activity Relationship
• Triazoles (chemical synthesis, chemistry, pharmacology, toxicity)